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The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy pp 113–125Cite as

Thymidylate Synthase and Fluorouracil

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 244))

Abstract

A knowledge of the catalytic mechanism of thymidylate synthase (TS), and its inhibition by 5-fluorodeoxyuridylate (FdUMP) was instrumental in developing the FUra-CF combination for cancer chemotherapy. The generation of the ideas which led to the current combination cleary demonstrates the importance of a fundamental knowledge of the interactions of inhibitors with their targets, and of how basic studies can be translated to clinical practice. The history of the development of the FUra-CF combination is a paradigm for the rational development of chemotherapeutic regimens. This report summarizes current knowledge of (a) the enzymology of the interaction of TS with FdUMP, (b) the 3-dimensional structure of TS, and (c) the effect of FUra on tRNA-uracil methyltranferase. Also, we suggest a possible molecular mechanism for the RNA effects of FUra.

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Author information

Authors and Affiliations

  1. Departments of Biochemistry and Biophysics and Pharmaceutical Chemistry, and the Biomolecular Resource Center, University of California, San Francisco, San Francisco, California, 94143, USA

    Kathryn M. Ivanetich & Daniel V. Santi

Authors
  1. Kathryn M. Ivanetich
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  2. Daniel V. Santi
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Editor information

Editors and Affiliations

  1. Roswell Park Memorial Institute, Buffalo, New York, USA

    Youcef Rustum  & John J. McGuire  & 

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© 1988 Plenum Press, New York

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Ivanetich, K.M., Santi, D.V. (1988). Thymidylate Synthase and Fluorouracil. In: Rustum, Y., McGuire, J.J. (eds) The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy. Advances in Experimental Medicine and Biology, vol 244. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-5607-3_11

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  • DOI: https://doi.org/10.1007/978-1-4684-5607-3_11

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4684-5609-7

  • Online ISBN: 978-1-4684-5607-3

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